Phosphonates lithium reaction

Two other features which have been found to influence the final reaction outcome are the nature of the reaction solvent and the individual metal counter ion. The effects of the first are varied, and the latter is also important since, for example, in reactions which involve dialkyl (2-oxoalkyl)phosphonates, lithium and magnesium ions tend to form com-plexes whereas sodium and potassium ions do not. In reactions between acetone and the anion from (prop-2-enyl)phosphonic bis(dimethylamide) and BuLi, the presence of zinc or cadmium ions alters the site of attack from only C ) to a mixture of C(,) and C ) in the ratio 3 1. Dialkyl (lithioalkyl)phosphonates which lack complexing functions may be rather unstable, or may dimerize within minutes at 0... 

The reactions of dimethyl methylphosphonate and the corresponding carbanion in the gas phase have been investigated. The carbanion displays a similar range of reactions to those encountered in solution, including olefmation with carbonyl compounds. The effect on olefin stereochemistry of a variety of conditions in reactions of a-phosphono lactones (e.g. 129) with ethanal and propanal has been studied and the results applied in syntheses of integerrinecic acid and senecic acid lactones. Yet further minor modifications of the conditions for phosphonate-olefination reactions, involving the use of lithium hydroxide as the base, have been reported. ... 

Reaction of A-protected diethyl aspartate (130) or glutamate (131) with lithium trialkylphosphonoacetate in the presence of DIBALH leads to selective formation of the A-protected y-amino-a,P-unsaturated dicarboxylates (132) as the major product. 3-(Phosphonomethyl)cyclo-pentenones (133) and -hexenones (134) are the products of the reaction of dimethyl succinate and dimethyl glutarate, respectively, with excess dimethyl (lithiomethyl)phosphonate presumably via two phosphonomethylations followed by an intramolecular olefmation. Examples of the many phosphonate olefmation reactions carried out include the synthesis of (2E, 4Z)-4-aminoalkadienoates (135), 2-aryloxy-3-phenylpropenoates (136), and isoxazoles (137). ... 

An aza-Darzens reaction, involving the addition of chloromethylphosphonate anions to enantiopure N-sulfinimines, has also been developed by Davis and others for the asymmetric synthesis of aziridine-2-phosphonates [81-84], As an example, treatment of the lithium anion generated from dimethyl chloromethylphos-phonate (93 Scheme 3.30) with N-sulfmimine (Ss)-92 gave the a-chloro-P-amino phosphonate 94, which could be isolated in 51% yield. Cyclization of 94 with n-BuLi gave cis-N-sulfmylaziridine-2-phosphonate 95 in 82% yield [81],... 

The reaction of 1,2-dithiolanes with 2- and 4-picolyllithium has been examined <96PS(112)101> and the reactions of thioanhydrides such as 94 with both thiols <95JOC3964> and amines <96TL5337> have been reported. Treatment of 1,2-dithiolium salts with lithium or thallium cyclopentadienide results in formation of a variety of bi-, tri- and tetracyclic products <96LA109>. Reaction of 95 with trimethyl phosphite gives some of the desired coupling product but also the phosphonates 96 <96PS(109)557>. 

The reaction of the aldehyde 174, prepared from D-glucose diethyl dithio-acetal by way of compounds 172 and 173, with lithium dimethyl methyl-phosphonate gave the adduct 175. Conversion of 175 into compound 176, followed by oxidation with dimethyl sulfoxide-oxalyl chloride, provided diketone 177. Cyclization of 177 with ethyldiisopropylamine gave the enone 178, which furnished compounds 179 and 180 on sodium borohydride reduction. 0-Desilylation, catalytic hydrogenation, 0-debenzyIation, and acetylation converted 179 into the pentaacetate 93 and 5a-carba-a-L-ido-pyranose pentaacetate (181). 

An alternative procedure for effecting the condensation of phosphonoacetates is to carry out the reaction in the presence of lithium chloride and an amine such as diiso-propylethylamine. The lithium chelate of the substituted phosphonate is sufficiently acidic to be deprotonated by the amine.262... 

Phosphate-derived a-oxycarbanions can rearrange into a-hydroxy phosphonates. This class of rearrangement is known to proceed with retention of configuration at the carban-ion terminus. The enantioselective version of this rearrangement has been developed using a chiral lithium amide as a base (equation 115) . The reaction of benzyl dimethyl phosphate 182 with amide R,R)-63 in THF gave the hydroxy phosphonate (5 )-183 in 30% in enantioenriched form (52% ee). 

Dibromoethylene, irradiation of, 5 156 Dibromomethylarsonic acids, 44 221 Dibromomethylsulfonium salts, 35 262 Di-(-butyldichlorosiIane, reactions, with lithium phosphides, 31 181-186 Dibutyl phosphonic acid, in liquid-liquid extraction, 9 34-35, 36-37... 

A less common approach to the synthesis of phosphinates is the reaction of electrophilic phosphonates with carbon nucleophiles such as Grignard reagents or lithium enolates. For example, the phosphinic acid analogue 71 of the amino acid statine was synthesized by displacement of tert-butyl lithioacetate on a 5-phenyl phosphonothioate 70 (Scheme 23)d104l The racemic diastereomers of the 5-phenyl phosphonothioate were obtained in pure form, and the displacement of the phenylsulfanyl moiety was found to be stereospecific, although the stereocenter at phosphorus would later be lost on hydrolysis of the ester. A similar displacement reaction has been described using the p h osp h on och I ori d ate.1711... 

Hammerschmidt, F. Hanninger, A. Enantioselective deproto nation of benzyl phosphates by homochiral lithium amide bases. Configurational stability of benzyl carbanions with a dialkoxyphosphoryloxy substituent and their rearrangement to optically active a-hydroxy phosphonates. Chem. Ber. 1995, 328, 823-830. Avolio, S. Malan, C. Marek, I. Knochel, P. Preparation and reactions of functionalized magnesium carbenoids. Synlett 1999, 1820-1822. 

The next part of the present study concerns the oxidation of the phosphonate and thiophosphonate carbanions. Generally, this reaction was found to occur in two directions depending on the structure of the starting phosphonate and the reaction conditions. The lithium salts of thiophosphonate carbanions 5 give on treatment with oxygen the corresponding a-hydroxy thiophosphonates exclusi vely. 

As expected, the reaction of the lithium salts of phosphonates with oxygen results in the formation of dialkyl phosphoric acids-8 and carbonyl products i.e. the cleavage of the C-P bond takes place (, 5). However, when the halomagnesiurn salts of phosphonates Z were oxidized, a-hydroxyphosphonates 2 were formed. 

Reactions of vinylphosphonates j2 with an equimolar amount of lithium dialkylcuprates J result in the formation of complexes 3 containing two different organic ligands. These complexes react with electrophiles in various ways. In each of them a diverse ligand plays the role of a nucleophile. Hydrolysis of 3 or alkylation with alkyl halides affords the corresponding phosphonates k and 5 comprising extended saturated carbon chains bonded to phosphorus. However, in a number of reactions with aldehydes, the complexes 3 were found to undergo almost completely selective transformation into carbinols 6... 

Polycondensation reactions of 2-chloroalkyl phosphates or phosphonates to obtain products having a controllable degree of condensation and low acid or latent acid contents were accomplished in our laboratory using catalysts such as quaternary ammonium salts, amines, amides, sodium carbonate, or lithium chloride (5). Reduction of the temperature diminished the... 

Lithium chloride (2.6 g) is dissolved in THF (170 mL). Dimethyl-(2-oxo-4-phenylbutyl)phosphonate (7.87 g) and triethylamine (4.3 mL) are added. The mixture is stirred and cooled to -10°C. A solution of the Corey aldehyde benzoate, (lS,5R,6R,7R)-6-formyl-7-(benzyloxy)-2-oxabicyclo[3.3.0]octan-3-one (8.42 g) in THF (75 mL) is added to the reaction mixture over three hours. The resulting mixture is stirred for 18 hours at -10°C. At the end of this time, methyl t-butyl ether (MTBE) (100 mL) is added and the mixture warmed to 0-20°C. Sodium bisulfite (38%, 100 mL) is added and the two-phase mixture was stirred for 10 min. The phases are separated and the organic phase is washed with saturated aqueous sodium bicarbonate solution (100 mL). The organic phase is separated and concentrated under reduced pressure to a volume of <100 mL. Ethyl acetate (200 mL) is added and the... 

As outlined in Scheme 28, the synthesis of the P-ketophosphonate 131 began with a one-pot anh -aldol/reduction step between ethyl ketone 101 and aldehyde 133, giving the 1,3-syn diol 134 (>30 ldr) [130, 132-136, 145, 146], The diol 134 was then converted into the carboxylic acid 135 in six steps. Completion of the subunit 131 required conversion into the acid chloride and reaction with the lithium anion of methyl-(di-l,l,l-trifluoroethyl)-phosphonate. The C9-C24 aldehyde 132 was prepared in two steps from 136, an intermediate from previous routes [55-58], The Still-Gennari-type coupling of 131 and 132 was readily achieved via treatment with... 

The reaction of N-tosyl vinyl sulfoximines 236 with lithium cyanide in DMF at room temperature for 1 h gave the vinyl nitriles 254 in good yields.117 Treatment of 236 with lithium dimethylphosphonate in THF at -78 °C to room temperature gave moderate yields of the vinyl phosphonates 255.117 These yields could be improved to 54-64% by isolation of the initial Michael adducts by quenching these reactions at -20 °C and then treatment of these products with sodium methoxide in methanol at reflux. These reactions proceed via the intermediates 256 and 257. 

The reaction afforded the tandem cyclization product 170 as a mixture of two separable isomers together with an a,p-unsaturated cyclic bisphosphonate, which is formed by a direct deprotonation of the vinylic a-proton of 168 and subsequent intramolecular Michael cyclization. The authors described the formation of 170 by the conjugated addition of 168 to 2.2 equivalents of PhLi and subsequent intramolecular Michael reaction in the intermediate 169. It is likely that coordination of the lithium atom to the oxygens of the phosphonates favors formation of the /raw.v-isomer. As shown in Scheme 52, the reactions with bulky naphthyllithiums gave only the fraws-170 isomer. This novel methodology can provide a rapid entry into a variety of cyclic bisphosphonates in good stereoselectivity. 

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